The host response to burns and trauma is a collection of biological and pathological processes that depends critically upon the regulation of the human metabolic response. Over the past 28 years of 50 funding, our Center has had a tremendous and unique research opportunity to study the physiology of metabolism after injury. Since its inception, the Center has focused on the metabolic aspects of the patient's immuno-inflammatory reaction to injury. In this competing renewal application, the first project, which has been a part of the Center for the past 28 years, addresses key amino acid relationships at the whole body level. The second project, which was added approximately 8 years ago, addresses the important issue of individual organ contributions as they relate to what can be measured at the whole body level. The third project, which was added 5 years ago, addresses the proximal aspects of insulin receptor dysfunction post-injury. Our newest project expands our investigations in insulin receptor dysfunction by addressing abnormalities in more distal controlling events. To complement our expanding research endeavors, we have added exciting new advanced technologies that will provide more detailed knowledge in vivo and in vitro not previously possible. Thus, 4 projects are proposed: (1) amino acid interrelations and metabolism hypothesis and approach; (2) tissue specific metabolic response to injury; (3) molecular mechanisms of burn induced insulin resistance; and (4) muscle wasting in burns: pivotal role of Akt/PKB. These synergistic studies will interact within and be supported by 4 core resources, which provide technical, and analytical services. The Burn Trauma Center contains the following 4 cores: (1) Human Subjects Core; (2) Animal Research Core; (3) PET and mu/PET Facility Core; and (4) Mass and NMR Spectroscopy Facility Core.